The goal of this research is to examine the relationships between cellular growth status and cell function in an effort to understand factors which contribute to collagen and proteoglycan accumulation in the development of diabetic pathologies. Cultured normal human skin fibroblasts are established as actively growing, low passaged (young) cultures, and quiescent (serum-restricted) sparse or confluent cultures, or as cultures near terminal phase (senescence). Collagen and proteoglycan synthesis by these cultures is assessed by the incorporation of radioisotope from 3H-proline and from Na 35SO4 plus 3H-glucosamine, respectively, into macromolecules. The extrinsic regulation of these processes by insulin and hydrocortisone is of specific interest. The involvement of cyclic AMP as a possible obligatory intrinsic regulator is examined by studies of growth and macromolecule accumulation in the presence of prostaglandin E2 with or without the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine.